Journal article
Normal electrophysiological and behavioral responses to ethanol in mice lacking the long splice variant of the γ2 subunit of the γ-aminobutyrate type A receptor
Neuropharmacology, Vol.38(2), pp.253-265
1999
DOI: 10.1016/S0028-3908(98)00177-4
PMID: 10218866
Abstract
The
γ subunit of the
γ-aminobutyric acid type A receptor (GABA
A-R) is essential for bestowing both normal single channel conductance and sensitivity to benzodiazepines on native GABA
A-Rs. The long splice variant of the
γ2 subunit (
γ2L) has been postulated to be essential in mediating the modulatory actions of ethanol at the GABA
A-R. In order to evaluate this hypothesis, gene targeting was used to delete the 24bp exon which distinguishes
γ2L from the short splice variant (
γ2S). Mice homozygous for this exon deletion (
γ2L
−/−) are viable and indistinguishable from wild-type (
γ2L
+/+) mice. No
γ2L mRNA was detected in these mice, nor could
γ2L-containing GABA
A-R protein be detected by specific antibodies. Radioligand binding studies showed the total amount of
γ2 subunit protein to be not significantly changed, suggesting that
γ2S replaces
γ2L in the brains of the knockout animals. Electrophysiological recordings from dorsal root ganglion neurons revealed a normal complement of functional receptors. There was no difference in the potentiation of GABA currents by ethanol (20–200 mM) observed in neurons from
γ2L
+/+or
γ2L
−/− mice. Several behavioral effects of ethanol, such as sleep time, anxiolysis, acute functional tolerance, chronic withdrawal hyperexcitability and hyperlocomotor activity were also unaffected by genotype. It is concluded that
γ2L is not required for ethanol’s modulatory action at the GABA
A-R or whole animal behavioral effects.
Details
- Title: Subtitle
- Normal electrophysiological and behavioral responses to ethanol in mice lacking the long splice variant of the γ2 subunit of the γ-aminobutyrate type A receptor
- Creators
- Gregg E Homanics - Department of Anesthesiology/Critical Care Medicine, W1356 Biomedical Science Tower, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USANeil L Harrison - Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637, USAJoseph J Quinlan - Department of Anesthesiology/Critical Care Medicine, W1356 Biomedical Science Tower, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USAMatthew D Krasowski - Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637, USACaroline E.M Rick - Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637, USAAngel L de Blas - Division of Molecular Biology and Biochemistry, University of Missouri, Kansas City, MO 64110-2499, USAAshok K Mehta - Division of Molecular Biology and Biochemistry, University of Missouri, Kansas City, MO 64110-2499, USAFrank Kist - Department of Anesthesiology/Critical Care Medicine, W1356 Biomedical Science Tower, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USARobert M Mihalek - Department of Anesthesiology/Critical Care Medicine, W1356 Biomedical Science Tower, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USAJerome J Aul - Department of Anesthesiology/Critical Care Medicine, W1356 Biomedical Science Tower, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USALeonard L Firestone - Department of Anesthesiology/Critical Care Medicine, W1356 Biomedical Science Tower, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
- Resource Type
- Journal article
- Publication Details
- Neuropharmacology, Vol.38(2), pp.253-265
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/S0028-3908(98)00177-4
- PMID
- 10218866
- ISSN
- 0028-3908
- eISSN
- 1873-7064
- Language
- English
- Date published
- 1999
- Academic Unit
- Pathology
- Record Identifier
- 9984046834502771
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